Reports of lung injuries from
e-cigarettes splash across the news these days, but the nicotine-delivery
devices are also spawning a quieter worry: whether users risk long-term health
effects that may not manifest for decades. Studies in animals and people are
now starting to probe whether e-cigarettes pose chronic risks to the lungs and
cardiovascular system and how the chemicals they contain might disrupt healthy
biology.
E-cigarettes are battery-powered devices containing nicotine and
other substances, such as solvents, that dissolve the nicotine and flavourings
that enhance their appeal. Heat converts the mix into an aerosol that users
inhale. Manufacturers tout e-cigarettes as tools to help smokers quit, although
data are mixed. But one thing is clear. Millions
of young people who didn't smoke cigarettes have taken up vaping. And given
that e-cigarettes vary more than conventional cigarettes in their chemical
composition, "We're asking medical science to do a huge, heavy lift"
to pinpoint health impacts across people, says James Stein, a preventive
cardiologist at the University of Wisconsin in Madison.
He, and others, believe they have no choice but to try. This month,
the National Heart, Lung, and Blood Institute gave a boost to studies of acute
and chronic effects when it announced supplemental funds for ongoing
e-cigarette research, on which the institute spent $23 million this year.
E-cigarettes have been around in some
form for decades but began to soar in popularity about 5 years ago, thanks to
thousands of flavouring options and new delivery methods that more closely
mimic smoking. Today, about 13 million
people in the United States use them, as do millions more worldwide. In March,
one hazard emerged when acute lung injuries began to strike; U.S. cases now
approach 2300, with 47 deaths.
"We were all taken by surprise"
by those lung injuries, says Peter Shields, a medical oncologist who
specializes in lung cancer at Ohio State University's Comprehensive Cancer Centre
in Columbus. They look unlike anything seen in cigarette smokers. Health
officials now suspect the injuries are linked to a vitamin E oil added to
e-cigarettes containing tetrahydrocannabinol, better known as THC.
Animal studies are already yielding clues about longer term effects
of e-cigarette use. In September, a paper in “The Journal of Clinical
Investigation” described mice exposed to e-cigarettes for 4 months, nearly
one-quarter of their life span. Farrah Kheradmand, a pulmonologist at Baylor
College of Medicine in Houston, Texas, who led the work, says that, at first,
"There was absolutely no emphysema, nothing" in the animals that
inhaled aerosol from e-cigarettes. That finding jibes with earlier research
showing combustion products are the cause of airway inflammation in smokers.
Then Kheradmand's graduate student
Matthew Madison showed her slides of the animals' lung tissue. Farrah did a double take. Immune cells called macrophages were swollen
with fat, an abnormality. Kheradmand
guessed at first that the cells had gorged on vegetable glycerine, which is
used as a solvent in vaping liquids. But
when the scientists cracked open the macrophages, they found they were
mistaken. "I couldn't sleep at night," Kheradmand says. "Where
is this fat coming from?"
Further experiments revealed a likely explanation. Macrophages protect the body from infections,
but they also help recycle lung surfactant, a mix of proteins and lipids that
coats the inside of lung air sacs and aids gas exchange. Vegetable Glycerine and another solvent in
e-cigarettes, propylene glycol, are "capable of not only dissolving
nicotine, but dissolving anything that comes their way, including the
surfactant," Kheradmand says, and her work suggests the macrophages were
filled with the type of fat in surfactant. Affected mice seemed healthy, but
when Kheradmand exposed them to a flu virus, those with swollen macrophages
died, suggesting their ability to battle infection had weakened.
Another vexing concern is whether, like smoking, vaping can lead to
cancer. Scientists believe e-cigarettes are likely to be less carcinogenic than
tobacco, but last month, a team from New York University School of Medicine in
New York City reported in the “Proceedings of the National Academy of Sciences”
that mice exposed to e-cigarettes for 54 weeks had an increased risk of lung
cancer and showed changes in bladder cells that presage cancer there.
No one knows whether the mouse findings will translate to people. But they reveal "some of the things we
should be looking for," says Thomas Eissenberg, a psychologist who
co-directs the “Centre for the Study of Tobacco Products” at Virginia
Commonwealth University in Richmond, and serves as a paid consultant in
litigation against the tobacco and e-cigarette industries.
Eissenberg is among those pushing for more human studies. He has
applied for funding to work with colleagues who would perform bronchoscopies on
healthy e-cigarette users and healthy controls. Unlike, say, the skin or the
gut, which are adapted to manage outside assaults, "The lungs don't have a
powerful defence mechanism," he says. "Once things get into the
lungs, they can cause a lot of trouble." Eissenberg wants to look for the
lipid-filled macrophages that Kheradmand saw in animals. And, he adds, "I'm worried about the
throat and the upper airways." Vegetable glycerine and propylene glycol
can dry up tissues, and they're being inhaled across "membranes that are
trying to be kept moist," Eissenberg says. "I wonder what the
long-term effects of that aridity are going to be."
Shields is one of few researchers who has already probed human
lungs for e-cigarettes' effects. Last month, his group published a paper in “Cancer
Prevention Research” that compared 15 healthy volunteers who used e-cigarettes
without nicotine for 4 weeks with 15 people who never smoked or vaped. (He did
the study before concerns about acute lung injuries surfaced.) Bronchoscopies on the vaping volunteers showed
minimal but measurable signs of inflammation in lung tissue and lung fluid. He
is now recruiting for a larger trial of 145 people, to include smokers
transitioning to e-cigarettes, as well as long-term e-cigarette users. It will look for markers of inflammation; gene
expression patterns; the balance of bacteria in the lungs, mouth, and throat;
and other signs of lung health and disease. "I have no idea what we're
going to see," Shields says.
Because cigarette smoking causes
cardiovascular disease, researchers wonder whether vaping has similar effects.
A study this month in the “Journal of the American College of Cardiology” found
some improvements in heart health among 74 smokers who switched to
e-cigarettes. But both habits deliver a host of chemicals that are absorbed
across the lining of the lungs. And concerns remain about non-smokers who take
up the habit, as well as smokers who try vaping to quit their habit but end up
using both forms of nicotine.
Stein is now recruiting 440 volunteers, all of whom either use
e-cigarettes exclusively, smoke and use e-cigarettes, or do neither. His team
is gathering physiological measurements before and after vaping or smoking,
including heart rate, blood pressure, artery-thickness and stiffness, and
aerobic function while running on a treadmill. The researchers will also
collect data on the e-cigarettes themselves, to see whether different products
vary in their health effects.
It was decades before science laid bare the long-term risks of
cigarettes to human health. Stein and others are hoping that for e-cigarettes,
that timeline will be far shorter. Right now, he says, "We have no idea
what the harm is."
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